Compositions, methods, and development of arid4b inhibitors

Abstract

The present disclosure generally relates to classes of compounds that bind the chromo-barrel domain of AT-rich interactive domain 4B (ARID4B). In some aspects, the compounds are of the Formula (II) as described herein, or a diamine composite thereof as set forth in Formula III herein. In some aspects, the compound is selected from compounds 1a, 1b, 1c, 1d, 1e, 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h, 2i, 2j, (as described herein) or combinations thereof. The present disclosure further considers administration of the compounds to target ARID4B in cells and for the treatment of cancerous breast tissue cells.

1 . An ARD150 derivative compound comprising the structure as set forth in Formula (II), 
       
         
           
           
               
               
           
         
       
       or a salt thereof
 wherein the spacer is null or —OCH 2 ; 
 R 1  is null, H, or CH 3 ; 
 R 2  is H or CH 3 ; and, 
 R 0  is selected from: 
 
       
         
           
           
               
               
           
         
       
       or a piperazine with the nitrogen of the depicted amide. 
     
     
         2 . The ARD150 derivative compound of  claim 1 , wherein the compound is selected from 1a-1e: 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         3 . The ARD150 derivative compound of  claim 1 or 2 , wherein the compound comprises 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         4 . The ARD150 derivative compound of  claim 1 , wherein the composition of Formula II bookends a diamine with a basic structure as set forth in Formula III: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The ARD150 derivative compound of  claim 4 , wherein each R3 is independently null, C 6 H 5 OC 6 H 5 CH 2 , or CH 3 . 
     
     
         6 . The ARD150 derivative compound of  claim 4 , wherein X is null, O, or S—S. 
     
     
         7 . The ARD150 derivative compound of  claim 4 , wherein the diamine is selected from the following structures: 
       
         
           
           
               
               
           
         
       
     
     
         8 . The ARD150 derivative compound of  claim 7 , wherein the bookended or symmetrical compounds are set forth in Formula IV: 
       
         
           
           
               
               
           
         
         wherein each spacer is independently null or OCH 2 ; 
         each R 1  is independently null, H, or CH 3 ; 
         each R 2  is independently H or CH 3 ; 
         each R3 is independently null, C 6 H 5 OC 6 H 5 CH 2 , or CH 3 ; and, 
         X is null, O, or S—S. 
       
     
     
         9 . The ARD150 derivative compound of  claim 7 , wherein the compounds is selected from compounds 2a-2f as follow: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         10 . The ARD150 derivative compound of  claim 1 , wherein the compounds comprises 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         11 . The ARD150 derivative compound of  claim 1 , wherein the compound comprises 
       
         
           
           
               
               
           
         
       
       or a salt thereof. 
     
     
         12 . A pharmecutical composition comprising the compouind of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         13 . The pharmacueitcla composiiton of  claim 12 , further compriusing an excipient. 
     
     
         14 . A method for targeting AT-rich interactive domain 4B (ARID4B) in a cell, comprising administering the ARD150 derivative compound of  claim 1  to a cell. 
     
     
         15 . The method of  claim 14 , wherein the cell is a cancer cell. 
     
     
         16 . The method of  claim 14 , wherein the cell is in vivo. 
     
     
         17 . A method for treating cellular dysplasia in breast tissue of a subject comprising administering the compound of  claim 1  to the subject. 
     
     
         18 . The method of  claim 17 , wherein the compound is administered by a route selected from parenteral, topical, intravenous, oral, subcutaneous, sublingual, intraarterial, intradermal, transdermal, rectal, intracranial, intrathecal, intraperitoneal, intranasal; vaginally; intramuscular route or as inhalants.